Optimize Risk Assessment for Incident and Recurrent Atherosclerotic Cardiovascular Disease

最近美国心脏协会（AHA）和美国心脏病学会（ACC）胆固醇指南 将动脉粥样硬化性心血管疾病（ASCVD）风险评估置于决策的中心， 开始和给予降脂治疗，包括他汀类药物、依折麦布和PCSK 9抑制剂。 尽管如此，关于该指南如何有效地指导药物治疗仍然存在争议。 他们将获得很大的绝对ASCVD风险降低获益。对于初级预防，2018年AHA/ACC 指南引入了风险增强因素的概念，以确定风险高于 通过合并队列方程（PCE）预测。风险增强因素的存在支持以下决定： 在临界和中等风险患者中开始或加强他汀类药物治疗。然而，该指南确实 没有量化风险增强因素对个体10年风险的影响， 或不治疗由风险增强因素最终主观知情。健康问题社会决定因素 （SDOH）是重要的ASCVD危险因素。PCE系统性地低估了以下个体的风险： 社会贫困;然而，社会发展部不包括在PCE中，也不被视为风险增加因素， 现行准则。此外，PCE在西班牙裔和亚洲人中的表现值得怀疑， 美国增长最快的少数民族。对于二级预防，2018年指南建议高- 2400万确诊ASCVD的美国成人接受他汀类药物强化治疗，使用依折麦布和PCSK 9 推荐用于复发性ASCVD风险极高的亚组的抑制剂，定义为多次ASCVD病史 主要ASCVD事件或1起主要事件伴多种高风险状况。然而，最近的证据表明， 这一定义可能会将太多的人（>50%）归类为具有非常高的风险。此外，妇女， 种族/少数民族，以及那些有不良SDOH的人可能有更高的复发ASCVD的风险，但那些 当定义复发性ASCVD的极高风险时，当前指南未考虑这些因素。 为了解决文献和指南中的这些差距，我们的研究建议：1）量化 存在或不存在每种风险增强因素（包括SDOH、西班牙裔和亚裔亚组），以及 它们的组合改变了超出PCE预测的10年ASCVD风险; 2）确定 优化了对复发ASCVD事件极高风险个体的区分;以及3）比较 选择个体进行降脂治疗对美国成年人健康、经济和健康公平性的影响 根据目标1和2中确定的方法与2018年胆固醇指南中确定的方法进行治疗。 这项研究将开发提高美国成年人胆固醇治疗指南精度的方法， 并帮助直接治疗少数民族亚组和群体的高负担的不利SDOH谁有 ASCVD风险高，但目前的国家胆固醇指南可能不推荐治疗。结果 这项研究将为未来的指南提供信息，改善心血管结局，缩小健康不平等。

Recent American Heart Association (AHA) and American College of Cardiology (ACC) cholesterol guidelines put atherosclerotic cardiovascular disease (ASCVD) risk assessment at the center of decision-making for initiating and dosing of lipid-lowering therapies including statins, ezetimibe, and PCSK9 inhibitors. Nonetheless, there remains controversy regarding how efficiently this guideline directs medication to those who will receive a large absolute ASCVD risk reduction benefit. For primary prevention, the 2018 AHA/ACC guideline introduced the concept of risk-enhancing factors to identify individuals who have a risk higher than predicted by the pooled cohort equations (PCE). The presence of risk-enhancing factors supports a decision to initiate or intensify statin therapy in patients with borderline and intermediate risk. However, the guideline did not quantify how much a risk-enhancing factor changes an individual's 10-year risk, making decisions to treat or not to treat informed by the risk-enhancing factors ultimately subjective. Social determinants of health (SDOH) are important ASCVD risk factors. The PCE systematically underestimates risk for individuals who are socially deprived; however, SDOH are not included in the PCE or considered as risk-enhancing factors in the current guidelines. Additionally, the PCE's performance is questionable in Hispanics and Asians, the two fastest growing minority groups in the US. For secondary prevention, the 2018 guideline recommends high- intensity statin therapy for the 24 million US adults with established ASCVD, with ezetimibe and PCSK9 inhibitors recommended for a subset with a very high risk for recurrent ASCVD, defined by a history of multiple major ASCVD events or one major event with multiple high-risk conditions. However, recent evidence suggests that this definition may classify too many individuals (>50%) as having very high risk. Additionally, women, racial/ethnic minorities, and those with adverse SDOH may have a higher risk for recurrent ASCVD, but those factors were not considered in the current guideline when defining very high risk of recurrent ASCVD. To address these gaps in the literature and guidelines, our study proposes to 1) quantify how much the presence or absence of each risk-enhancing factor (including SDOH and Hispanic and Asian subgroups) and their combinations change 10-year ASCVD risk beyond PCE predictions; 2) determine the algorithm that optimizes the discrimination of individuals at very high risk for a recurrent ASCVD event; and 3) compare the health, economic, and health equity impact among US adults of selecting individuals for lipid-lowering therapies according to approaches identified in Aims 1 and 2 vs. in the 2018 cholesterol guideline. This study will develop approaches that improve the precision of cholesterol treatment guidelines in US adults, and help direct treatment to ethnic subgroups and groups with a high burden of adverse SDOH who have a high ASCVD risk but may not be recommended treatment by current national cholesterol guidelines. Findings from this study will inform future guidelines, improve cardiovascular outcomes, and narrow health inequities.